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Hematology CPC

This case study presents a 43-year-old man who developed neurological complications after undergoing bariatric surgery. The complications include peripheral neuropathy, macrocytic anemia, and myelodysplastic syndrome. This article discusses the potential risks and complications associated with bariatric surgery.

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Hematology CPC

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  1. Hematology CPC Bao Le, DO Internal Medicine October 9 , 2007

  2. Objectives • Presenting a case • Bariatric surgery • Neurologic complications of Bariatric surgery • Peripheral neuropathy • Macrocytic anemia • Myelodysplastic syndrome • Conclusion

  3. Case • CC: Sore throat. • HPI: A 43 y/o man presents to the ER with: • A 3-day history of mouth and throat pain associated with a white coating. • Temperature of 102 F at home with chills. • Progressively fatigued over past 5 months. • Overt dyspnea on exertion with walking 10 yards. • Progressive numbness of his fingers and toes ascending to mid shin and mid forearm over one year. • He denies: • Changes in mentation or tongue soreness. • Bright red blood per rectum or black tarry stools.

  4. ●PMH: Bariatric surgery at the age of 25, in 1987. Weighed 541 lbs prior to the surgery. PSH: Bariatric surgery. Family hx: No blood dyscrasias. Positive for obesity. Social hx: Worked as a laborer. No heavy metal exposure. 10 pack/year tobac history. Less than 1 drink EtOH/day. Medications: B12 injections. Iron 325 mg BID. MVI. ROS: Pertinent per HPI. Case (Cont’)

  5. Case (Cont’) • Physical Exam: • VS: 110/75, 105, 97% RA, 101.2 F, 240 lbs, 6’1” • GEN: toxic, uncomfortable, no dyspnea with conversation. • HEENT: oral mucosa coated with thrush, tongue appears normal, non-icteric sclera, conjuctiva was pale. • NECK: prominent carotid pulse, no thrill or bruit, no lymphadenopathy. • CV: tachycardic, S1 S2, no m/g/rubs. • RESP: clear. • ABD: mod obese, no TTP, no organomegaly.

  6. Case (Cont’) • Physical Exam (cont’): • EXT: chronic venous insufficiency changes. • DERM: no rashes. • PSYCH: appropriate. • NEURO: • distal reflexes decreased. • distal sensation decreased. • able to ambulate. • normal speech pattern.

  7. LAB: G: 20%, M: 15%, L: 65% MCV: 108, RDW: 13 Ferritin: < 10 (39-150) B12: > 700 pg/mL MMA: not elevated Folic acid: normal LDH: 210 (60-200) Liver and Renal: normal PBS: Severe leukopenia Few (< 1 per HPF/avg) hypersegmented neutrophils No blasts Macrocytic RBC without fragmentation Bone Marrow: Hypercellular: 70% Trilineage dysplasia Ringed sideroblasts < 5% blasts Cytogenetics: normal Case (Cont’) 5.6 1000 65000

  8. Case Overview Neurological deficits Sore throat DOE/Fatigue 43 y/o man Constitutional symptoms Hematologic abnormalities Pancytopenia Bariatric surgery

  9. Obesity and Bariatric Surgery • According to 2000 US Census: 63 million adult Americans with obesity, BMI ≥ 30, and 10.5 million with morbid obesity, BMI ≥ 40. • Annual obesity-related medical expenditures were substantial. • The rise in the prevalence of obesity is associated with increases in the prevalence of obesity comorbidities. • The loss of life expectancy due to obesity is profound. • In 1991, NIH established bariatric surgery guidelines: BMI ≥ 40 or ≥ 35 in the presence of significant comorbidities.

  10. Gastrointestinal Tract Calcium Iron, Phosphorus, zinc Copper, Vitamins B12, Zinc Copper, Phosphorus Vitamins

  11. Bariatric surgery techniques

  12. The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. • Age 37-60, BMI > 34 for male, BMI > 38 for female. • Conventional treatment: 2037 • Bariatric surgery: 2010 • Average follow-up: 10.9 years • Surgical group had a hazard ratio of 0.76 compared to control group ( 95% confidence interval, 0.59 – 0.99, P = 0.04)

  13. 136 articles and 22094 patients. • JAMA, October 13, 2004 - Vol 292. • Results: • Resolution of DM: 76.8 % • Resolution of HTN: 61.7 % • Improvement of lipid: 83 % • Resolution of OSA: 85.7 %

  14. Neurologic Complication of Bariatric Surgery • Encephalopathy • Behavior abnormalities • Cranial nerve palsies • Ataxia • Seizure • Myelopathy • Plexopathy • Mononeuropathy • Myopathy • Myotonia • Peripheral neuropathy

  15. Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN. • Neurology 2004; 63:1462-1470. • Retrospective review study, 1985 - 2001. • Open Cholecystectomy: 300; BS: 435. BS: 16 % • Peripheral Neuropathy: P < 0.001 Open Chol: 3 %

  16. Neuropathic characteristics of PN after BS Sensory-predominant PN Insidious onset Chronic course Distal LE/UE Mononeuropathy Carpal Tunnel Syndrome Radiculoplexus neuropathy Lumbosacral Cervical

  17. Risk factors for PN after BS: • A greater absolute weight loss • A faster rate of weight loss • A lower postsurgery BMI • Lower serum albumin • Lower transferrin concentrations • Prolonged postsurgery GI symptoms • Less MVI and Ca supplement • Not attending nutritional clinics

  18. Inflammatory/Immune-Mediated Neuropathies Guillain-Barre syndrome Chronic inflammatory demyelinating polyradiculoneuropathy Vasculitic neuropathy Sarcoid neuropathy Neuropathies associated with connective tissue disease Toxic Neuropathies Drugs, metals, alcohol Neuropathies Associated with Cancer Remote effects of cancer Direct tumor infiltration Symmetric Polyneuropathies

  19. Inherited Neuropathies Hereditary motor sensory neuropathies Giant axonal neuropathy Porphyric neuropathies Lysosomal enzyme deficiency (Fabry disease) Lipoprotein disorders Neuropathies Associated with Infection HIV Leprosy Lyme disease Neuropathies Associated with Organ System Failure Kidney, lung, liver Critical illness polyneuropathy Organ transplantation Diabetic Polyneuropathy Vitamin Deficiencies Cobalamin (B12) Vitamin E Thiamine (B1) Pyridoxine (B6) Symmetric Polyneuropathies

  20. Neurologic Manifestations of Cobalamin (B12) Deficiency • Distal paresthesias • Unsteady gait • Deficit in vibratory sensation and proprioception • Diffuse hyperreflexia • Loss of reflex at ankle • Neurobehavioral changes: apathy, irritability, memory loss.

  21. Neurologic Manifestations of Vitamin E Deficiency • Progressive gait ataxia • Night blindness • Loss of vibratory sensation and proprioception • Absent reflexes • Ptosis/Ophthalmoplegia • Dysarthric speech • Intention tremor

  22. Neurologic Manifestations of Thiamine (B1) Deficiency • Fatigue/Irritability • Distal paresthesias affecting feet with burning pain • Distal sensory loss • Hyporeflexia • Wernicke-Korsakoff syndrome: mental confusion, ataxia, ophthalmoplegia • Cerebellar degeneration

  23. Neurologic Manifestations of Pyridoxine (B6) Deficiency • Paresthesias in distal limbs • Gait instability • Distal areflexia with normal muscle strength • Lhermitte sign (Barber Chair Phenomenon) • EMG: • Absent or reduced sensory nerve potentials • Normal motor nerve conduction

  24. Gastrointestinal Tract Calcium Iron, Phosphorus, zinc Copper, Vitamins B12, Zinc Copper, Phosphorus Vitamins

  25. Department of Neurology and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. • Neurology 2004;63:33-39 • Chart review of 13 patients with known copper deficiency and neurologic deficits.

  26. 45 y/o woman Persistent LE paresthesias and difficulty ambulating PE: Marked pallor and palpable spleen Neuro: Hyperactive reflexes Markedly decreased vibratory sense LE Extremely ataxic gait Cognition normal BM: Hypercellular Ringed sideroblasts 45 y/o man 4-month hands and feet paresthesias Progressive weakness, exertional dyspnea, difficulty ambulating PE: Marked pallor and mild hepatosplenomegaly Neuro: Slow and clumsy toe tapping Decreased vibratory sensation and proprioception Marked truncal ataxia Brisk reflexes University of Oklahoma Health Science Center. Neurology 2002;59:1953-1456

  27. Copper Deficiency Causes Demyelination 2 Atoms of Copper O2 ↑ Superoxide Dismutase O2 H2O2 Oxidadive damages DNA Proteins Lipids Demyelination

  28. Drugs Alcoholism Reticulocytosis Liver disease Hypothyroidism Vitamin B12 deficiency Folate deficiency Multiple myeloma Aplastic anemia Acute leukemia Myelodysplastic syndrome Macrocytic Anemia Chemotherapeutic agents Diuretics Cyclophosphamide Triamterene Hydroxyurea Anticonvulsant agents Methotrexate Phenytoin Azathioprine Primidone Mercaptopurine Valproic acid 5-Fluoracil Anti-inflammatory Antiretroviral Sulfasalazine Zidovudine Stavudine Hypoglycemia Metformin Antimicrobials Pyrimethamine Sulfamethoxazole Trimethoprim Valacyclovir

  29. Myelodysplastic Syndrome • MDS comprises a heterogeneous group of malignant stem cell disorders characterized by dysplastic and ineffective blood cell production. • These disorders may occur de novo or arise years after exposure to potentially mutagenic therapy. • The precise incidence of de novo MDS is not known. • MDS manifests as symptomatic anemia (60-80%), neutropenia (50-60%), and thrombocytopenia (40-60%). • Clinical presentations: • Incidental findings on routine laboratory studies. • Fatigue, malaise, and a general sense of tiredness. • Petechiae, ecchymoses, nose and gum bleeding. • Fever or shock.

  30. Myelodysplastic Syndrome • Physical Exam: • Pale, petechiae, purpura • Hepatomegaly, splenomegaly, LN • Tachycardia, fever • PBS: • Macrocytic with oval-shaped RBC • Basophilic stippling, Howell-Jolly bodies • Neutropenia • Thrombocytopenia • Bone Marrow: • Hypercellularity with trilineage dysplastic changes • Ringed sideroblasts • Cytogenetics: • Normal, 5q-, 7q-, 20q-, trisomy 8+

  31. FAB Criteria for MDS Subgroups

  32. Myelodysplastic Syndrome

  33. Myelodysplastic Syndrome

  34. Myelodysplastic Syndrome • Treatment: • Supportive care: • Transfusion as needed • Iron chelation • Low-intensity therapy: • Anemia: EPO ± G-CSF (ringed sideroblast and serum Epo levels < 500 mU/mL) • Neutropenia: G-CSF or GM-CSF • Thrompocytopenia: IL-11, thrombopoietin, danazol • 5-azacytidine • Immunosuppressive therapy: ATG and cyclosporine • Anti-TNF, anti-angiogenesis agents • High-intensity therapy: • Chemotherapy • Hemopoietic stem cell transplantation (HSCT)

  35. Copper Deficiency Central/peripheral neuropathy Copper Deficiency ? MDS Anemia Leukopenia

  36. Baylor College of Medicine, Houston, Tx; and the Department of Pathology, University of Alabama at Birmingham. • Blood, 15 August 2002. Vol 22, number 4: 1493-1495. • 44 y/o woman with h/o gastric resection with Billroth II for peptic ulcer who presents with macrocytic anemia and leukopenia. • WBC: 1.5 with 19% neutrophils, hemoglobin 6.4 g/dl, MCV: 102, platelet count: 192. • B12, folate, and ferritin were elevated. • PBS: macrocytic, oval shaped RBC • Bone marrow: dyserythropoiesis, dysmyelopoiesis, ringed sideroblasts, and prominent hemosiderin in plasma cell. • Cytogenetic studies were normal.

  37. She was diagnosed with MDS, FAB subtype refractory anemia with ringed sideroblasts (RARS). • Treated with G-CSF and EPO. • Referred for BM transplantation. • Treated with 6 weeks of IV copper chloride. • Normalized hematologic abnormalities and bone marrow aspiration.

  38. Department of Neurology, University of Michigan, MI. • Arch Neurol 2003: 60;1303-1306. • 46 y/o male c/o: • CP/SOB • Progressive numbness and weakness of both LE • Poor balance • Neurologic Exam: • Intact cranial nerves • Normal mentation • Brisk DTR’s in LE’s • Bilateral plantar flexor response • Markedly reduced vibratory sensation and propioception • Wide based gait

  39. Lab: • Hemoglobin: 7.9 g/dL • Copper: < 10 ug/dL (80 – 120 ug/dL) • Zinc: 184 ug/dL (80 – 120 ug/dL) • 24-hour urine copper: 0.04 mg/d ( 0.03 – 0.05 mg/d) • 24-hour urine zinc: 5.01 mg/d ( 0.24 – 0.4 mg/d) • Treatment: • Started copper supplement 2 mg/d • Normalize hematologic abnormalities • Worsening neurologic deficits • Increased to 8 mg/d • Improving neurologic deficits

  40. Hyperzincemia Induces Copper Deficiency ↑ Zinc ↑ Metallothionein Metallothionein competes Copper receptors in GI ↓ GI Copper Absorption Copper Deficiency

  41. Iron Metabolism Depends on Copper Copper (6 atoms) Ceruloplasmin Ferrous Iron Fe++ Ferric Iron Fe+++ Transferrin Apotransferrin Apo Tf Abnormal iron metabolism

  42. 82 of 3-5 day-old pigs: • Control with no iron • Control with PO iron • Control with IM iron • Exp with PO iron • Exp with IM iron • Study over 14 weeks

  43. Conclusion Abnormal iron metabolism Copper deficiency Peripheral polyneuropathy Myelodysplastic syndrome RARS Neutropenia Macrocytic anemia Thrombocytopenia Neutropenic fever Fatigue, DOE

  44. Lab/Study • Dr. Hurley: • Dr. Starr: • Copper and Ceruloplasmin Level • Complete iron panel • Dr. Clark: Blood and Urine Culture Rectal Exam!!! EMG

  45. References • Xylina T. Gregg, Vishnu Reddy, and Josef T. Prchal. Copper deficiency masquerading as myelodysplastic syndrome. Blood 2002; 100: 1493-1495. • P. Thaisetthawatkul, M.L. Collazo-Clavell, M.G. Sarr, J.E. Norell, and P.J.B. Dyck. A controlled study of peripheral neuropathy after bariatric surgery. Neurology 2004; 63: 1462-1470. • Katalin Juhasz-Pocsine, Stacy A. Rudnicki, Robert L. Archer, Sami I. Harik. Neurlogic complications of gastric bypass surgery for morbid obesity. Neurology 2007:68:1843-1850. • Jerry R. Mendell, John T. Kissel, David R. Cornblath. Diagnosis and Management of Peripheral Nerve Disorders. Oxford University Press, Inc. New York, NY, 2001. • Henry Buchwald, Yoav Avidor, Eugene Braunwald, Michael K. Jensen, Walter Pories, Kyle Fahrbach, Karen Schoelles. Bariatric Surgery. JAMA 2004;292:1724-1728. • Neeraj Kumar, John B. Gross, and Eric Ahlskog. Copper deficiency myelopathy porduces a clinical picture like subacute combined degeneration. Neurology 2004;63:33-39. • P Peter L. Greenberg, Neal S. Young, and Norbert Gattermann. Myelodysplastic Syndromes. Hematology 2002; 136-161. • G. Richard Lee, Sergio Nacht, John N. Lukens, and G. E. Cartwright. Iron Metabolism in Copper-Deficient Swine. The Journal of Clinical Investigation 1968; 47:2058-2069. • Florence Aslinia, Joseph J. Mazza, Steven H. Yale. Megaloblastic Anemia and Other Causes of Macrocytosis. Clinical Medicine & Research 2006;4: 236-241. • Edward H. Livingston. Complications of Bariatric Surgery. Surgical clinics of North America 2005;85:853-868. • C.I. Prodan, N.R. Holland, P.J. Wisdom, S.A. Burstein, S.S. Bottomley. CNS Demyelination Associated with copper Deficiency and Hyperzincemia. Neurology 2002;59:1453-1456. • Neeraj Kumar, John B. Gross, J. Eric Ahlskog. Myelopathy due to Copper Deficiency. Neurology 2003;61: 273-274. • Peter Hedera, John K. Fink, Paula L. Bockenstedt, George J. Brewer. Myelopolyneuropathy and Pancytopenia due to copper Deficiency and High Zinc Levels of Unknown Origin. Arch Neurol 2003;60:1303-1306.

  46. Thank you! Questions?

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